Sodium Bicarbonate → S-Ethyl O-(N3,N7,N12,N16-tetra(t-butoxycarbonyl)-3,7,12,16-tetraazahexadecanoyl oxy)methyl carbonothioate

HRID 1397113Notes

Reaction equation

HRID 1397113 reaction equation
[C:1](=[O:8])([O:5][CH2:6]I)[S:2][CH2:3][CH3:4].[C:9]([O:13][C:14]([N:16]([CH2:21][CH2:22][CH2:23][N:24]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:25][CH2:26][CH2:27][CH2:28][N:29]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:17][C:18]([OH:20])=[O:19])=[O:15])([CH3:12])([CH3:11])[CH3:10].C([O-])(O)=O.[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl.O.C(Cl)Cl>[C:1](=[O:8])([O:5][CH2:6][O:20][C:18](=[O:19])[CH2:17][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:21][CH2:22][CH2:23][N:24]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:25][CH2:26][CH2:27][CH2:28][N:29]([C:41]([O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[O:42])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[S:2][CH2:3][CH3:4]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 11006845N3,N7,N12,N16-Tetra(t-butoxycarbonyl)-3,7,12,16-tetraazahexadecanoic acidHCID 11436522(Ethylsulfanyl)(iodomethoxy)methanone

Product 1

HCID 86666527S-Ethyl O-(N3,N7,N12,N16-tetra(t-butoxycarbonyl)-3,7,12,16-tetraazahexadecanoyl oxy)methyl carbonothioateYield 92.3%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolventHCID 21908982Water methylene chlorideSolvent

Procedure

S-Ethyl O-iodomethyl carbonothioate (423 mg, 1.72 mmol) was added to a stirring mixture of 31 (1.13 g, 1.71 mmol), NaHCO3 (298 mg, 3.55 mmol) and tetrabutylammonium hydrogensulfate (588 mg, 1.73 mmol) in CH2Cl2/H2O (1:1, 17 mL) and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with CH2Cl2 (80 mL) and the aqueous layer was discarded. The organic layer was washed with saturated aqueous NH4Cl, saturated aqueous NaCl, dried over Na2SO4 then concentrated under reduced pressure. The residue was resuspended in Et2O, filtered and again concentrated under reduced pressure. The crude material was purified by silica gel chromatography (25%-60% EtOAc in hexanes over 10 column volumes) to give the colourless liquid 32 (1.23 g, 92%): 1H NMR (400 MHz, CDCl3): δ 1.32 (t, J=7.3, 3H), 1.41-1.47 (m, 40H), 1.61-1.75 (m, 4H), 2.89 (q, J=7.3, 2H), 3.10-3.31 (m, 12H), 3.92 (s, 4/7 of 2H, rotamer A), 4.01 (s, 3/7 of 2H, rotomer B), 5.84 (s, 2H).

Workup

  1. washThe organic layer was washed with saturated aqueous NH4Cl, saturated aqueous NaCl
  2. dry with materialdried over Na2SO4
  3. concentrationthen concentrated under reduced pressure
  4. filtrationfiltered
  5. concentrationagain concentrated under reduced pressure
  6. customThe crude material was purified by silica gel chromatography (25%-60% EtOAc in hexanes over 10 column volumes)

Sources & evidence

ORD record
ord-ef97f8d2e01b45db82fa8cc2c8a27706
Source dataset
uspto-grants-2014_12
Patent number
US08901072B2

Reaction notes

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